Many human cancers are now recognized to be the result of accumulated genetic lesions which culminate in the transformed malignant phenotype. As these disease states result from defined genetic mutations, gene therapy techniques may provide a rational basis for intervention. To this end, several distinct gen therapy strategies have been developed and employed. Ovarian cancer is ideally suited for application of gene therapy, given the poor overall outcome with conventional therapies in most instances. Therefore, it is our hypothesis that a variety of gene therapy strategies can be developed as rational therapeutic options in the context of ovarian cancer. This proposal will demonstrate the broad research and mentoring activities in gene therapy for ovarian cancer that are currently being conducted and those that are being planned by the candidate for this Midcareer Investigator award. Pursuant to this hypothesis the candidate intends to develop a Program for Ovarian Cancer Gene Therapy with emphasis on rapid translation of novel preclinical gene therapy strategies for ovarian cancer into human clinical trials and with emphasis on the mentoring and development of junior basic and clinical faculty in ovarian cancer gene therapy translational research. To facilitate these aims, the candidate also intends to enhance his fund of knowledge and skills in molecular biology, clinical study design and implementation, informatics, and manuscript and grant writing. Thus, by virtue of developing a new therapeutic paradigm for ovarian cancer and assisting with midcareer and junior faculty development, this award will make a substantial impact in gynecologic oncology, a specialty exclusively devoted to women's reproductive tract malignancies and in need of translational scientists.